Abstract
Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that regulates several processes important for hematologic cancer progression. S1P is generated by two sphingosine kinases, SphK1 and SphK2, and is exported outside the cell, where it activates specific cell surface S1P G-protein coupled receptors in autocrine/paracrine manner, coined "inside-out signaling". In this review, we highlight the importance of SphK1 and inside-out signaling by S1P in hematologic malignancy. We also summarize the results of studies targeting the SphK1/S1P/S1P receptor axis and the effects of the S1P receptor modulator, FTY720, in hematologic malignancy.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Fingolimod Hydrochloride
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Hematologic Neoplasms / drug therapy*
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Hematologic Neoplasms / enzymology
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Hematologic Neoplasms / metabolism*
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Humans
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Immunosuppressive Agents / pharmacology
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Immunosuppressive Agents / therapeutic use*
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Lysophospholipids / metabolism*
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Propylene Glycols / pharmacology
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Propylene Glycols / therapeutic use*
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Receptors, Lysosphingolipid / metabolism
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Sphingosine / analogs & derivatives*
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Sphingosine / metabolism
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Sphingosine / pharmacology
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Sphingosine / therapeutic use
Substances
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Immunosuppressive Agents
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Lysophospholipids
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Propylene Glycols
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Receptors, Lysosphingolipid
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sphingosine 1-phosphate
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Phosphotransferases (Alcohol Group Acceptor)
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sphingosine kinase
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Fingolimod Hydrochloride
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Sphingosine